Caspase-Cleaved Glial Fibrillary Acidic Protein Within Cerebellar White Matter of the Alzheimer\u27s Disease Brain

Although the cerebellum is generally thought of as an area spared of Alzheimer\u27s disease (AD) pathology, recent evidence suggests that balance and mobility dysfunction may be magnified in affected individuals. In the present study, we sought to determine the degree of pathological changes within the cerebellum utilizing an antibody that specifically detects caspase-cleaved GFAP within degenerating astrocytes. Compared to control subjects, application of this antibody, termed the GFAP caspase-cleavage product (GFAPccp) antibody, revealed widespread labeling in cerebellar white matter with little staining observed in grey matter. Staining was observed within damaged astrocytes, was often localized near blood vessels and co-localized with other markers of apoptosis including TUNEL and caspase-cleaved tau. Of interest was the association of beta-amyloid deposition in white matter together with GFAPccp in cerebellar AD sections. In contrast, utilizing the tangle marker, PHF-1, neuritic pathology was completely absent in AD cerebellar sections. It is suggested that the observed pathological changes found in the white matter of the cerebellum may contribute to the declined motor performance in AD

Identification of an Amino-Terminal Fragment of Apolipoprotein E4 that Localizes to Neurofibrillary Tangles of the Alzheimer’s Disease Brain

Although the risk factor for harboring the apolipoprotein E4 (apoE4) allele in late-onset Alzheimer’s disease (AD) is well known, the mechanism by which apoE4 contributes to AD pathogenesis has yet to be clarified. Preferential cleavage of the ApoE4 isoform relative to other polymorphic forms appears to be significant, as the resulting fragments are associated with hallmarks of AD. To examine the possible role of apoE4 proteolysis in AD, we designed a site-directed antibody directed at position D172, which would yield a predicted amino-terminal fragment previously identified in AD brain extracts. Western blot analysis utilizing this novel antibody, termed the amino-terminal apoE4 cleavage fragment (nApoE4CF) Ab consistently identified the predicted amino-terminal fragment (~18 kDa) in several commercially available forms of human recombinant apoE4 purified from E. coli. Mass spectrometry confirmed the identity of this 18 kDa fragment as being an amino-terminal fragment of apoE4. Immunohistochemical experiments indicated the nApoE4CF Ab specifically labeled neurofibrillary tangles (NFTs) in AD frontal cortex sections that colocalized with the mature tangle marker PHF-1. Taken together, these results suggest a novel cleavage event of apoE4, generating an amino-terminal fragment that localizes within NFTs of the AD brain

Genetic Studies of Sulfadiazine-resistant and Methionine-requiring \u3cem\u3eNeisseria\u3c/em\u3e Isolated From Clinical Material

Deoxyribonucleate (DNA) preparations were extracted from Neisseria meningitidis (four isolates from spinal fluid and blood) and N. gonorrhoeae strains, all of which were resistant to sulfadiazine upon primary isolation. These DNA preparations, together with others from in vitro mutants of N. meningitidis and N. perflava, were examined in transformation tests by using as recipient a drug-susceptible strain of N. meningitidis (Ne 15 Sul-s Met+) which was able to grow in a methionine-free defined medium. The sulfadiazine resistance typical of each donor was introduced into the uniform constitution of this recipient. Production of p-aminobenzoic acid was not significantly altered thereby. Transformants elicited by DNA from the N. meningitidis clinical isolates were resistant to at least 200 μg of sulfadiazine/ml, and did not show a requirement for methionine (Sul-r Met+). DNA from six strains of N. gonorrhoeae, which were isolated during the period of therapeutic use of sulfonamides, conveyed lower degrees of resistance and, invariably, a concurrent methionine requirement (Sul-r/Met−). The requirement of these transformants, and that of in vitro mutants selected on sulfadiazine-agar, was satisfied by methionine, but not by vitamin B12, homocysteine, cystathionine, homoserine, or cysteine. Sul-r Met+ and Sul-r/Met− loci could coexist in the same genome, but were segregated during transformation. On the other hand, the dual Sul-r/Met− properties were not separated by recombination, but were eliminated together. DNA from various Sul-r/Met− clones tested against recipients having nonidentical Sul-r/Met− mutant sites yielded Sul-s Met+ transformants. The met locus involved is genetically complex, and will be a valuable tool for studies of genetic fine structure of members of Neisseria, and of genetic homology between species

Entire curves avoiding given sets in C^n

Let $F\subset\Bbb C^n$ be a proper closed subset of $\Bbb C^n$ and $A\subset\Bbb C^n\setminus F$ at most countable ($n\geq 2$). We give conditions of $F$ and $A$, under which there exists a holomorphic immersion (or a proper holomorphic embedding) $\phi:\Bbb C\to\Bbb C^n$ with $A\subset\phi(\Bbb C)\subset\Bbb C^n\setminus F$.Comment: 10 page

Convergence of random zeros on complex manifolds

We show that the zeros of random sequences of Gaussian systems of polynomials of increasing degree almost surely converge to the expected limit distribution under very general hypotheses. In particular, the normalized distribution of zeros of systems of m polynomials of degree N, orthonormalized on a regular compact subset K of C^m, almost surely converge to the equilibrium measure on K as the degree N goes to infinity.Comment: 16 page

Heavy Water Obtained by the Combustion of Dried Biological Specimens

Dry, finely divided plant and animal tissues were oxidized by passage over hot copper oxide; the aqueous condensates were first distilled from potassium permanganate and then alone. If necessary, oxidation and distillation were repeated until there was no significant change in density. Densities were determined by a modification of the submerged magnetic float procedure, and the accuracy was one part per million. The specimens examined were practically all of the chief organs of cattle; yeasts; dairy products; and some parts of plants like corn and melons. The study is being extended to other biological specimens, normal and pathological

Immunolocalization of an Amino-Terminal Fragment of Apolipoprotein E in the Pick\u27s Disease Brain

Although the risk factor for apolipoprotein E (apoE) polymorphism in Alzheimer\u27s disease (AD) has been well described, the role that apoE plays in other neurodegenerative diseases, including Pick\u27s disease, is not well established. To examine a possible role of apoE in Pick\u27s disease, an immunohistochemical analysis was performed utilizing a novel site-directed antibody that is specific for an amino-terminal fragment of apoE. Application of this antibody, termed the amino-terminal apoE cleavage fragment (nApoECF) antibody, consistently labeled Pick bodies within area CA1 of the hippocampus in 4 of the 5 cases examined. Co-localization of the nApoECF antibody with PHF-1, a general marker for Pick bodies, as well as with an antibody to caspase-cleaved tau (TauC3) was evident within the hippocampus. While staining of the nApoECF antibody was robust in area CA1, little co-localization with PHF-1 in Pick bodies within the dentate gyrus was observed. A quantitative analysis indicated that approximately 86% of the Pick bodies identified in area CA1 labeled with the nApoECF antibody. The presence of truncated apoE within Pick bodies suggests a broader role of apoE beyond AD and raises the question as to whether this protein contributes to pathogenesis associated with Pick\u27s disease

Compressed gas domestic aerosol valve design using high viscous product

Most of the current universal consumer aerosol products using high viscous product such as cooking oil, antiperspirants, hair removal cream are primarily used LPG (Liquefied Petroleum Gas) propellant which is unfriendly environmental. The advantages of the new innovative technology described in this paper are: i. No butane or other liquefied hydrocarbon gas is used as a propellant and it replaced with Compressed air, nitrogen or other safe gas propellant. ii. Customer acceptable spray quality and consistency during can lifetime iii. Conventional cans and filling technology There is only a feasible energy source which is inert gas (i.e. compressed air) to replace VOCs (Volatile Organic Compounds) and greenhouse gases, which must be avoided, to improve atomisation by generating gas bubbles and turbulence inside the atomiser insert and the actuator. This research concentrates on using “bubbly flow” in the valve stem, with injection of compressed gas into the passing flow, thus also generating turbulence. The new valve designed in this investigation using inert gases has advantageous over conventional valve with butane propellant using high viscous product (> 400 Cp) because, when the valving arrangement is fully open, there are negligible energy losses as fluid passes through the valve from the interior of the container to the actuator insert. The use of valving arrangement thus permits all pressure drops to be controlled, resulting in improved control of atomising efficiency and flow rate, whereas in conventional valves a significant pressure drops occurs through the valve which has a complex effect on the corresponding spray

Bergman kernel and complex singularity exponent

We give a precise estimate of the Bergman kernel for the model domain defined by $\Omega_F=\{(z,w)\in \mathbb{C}^{n+1}:{\rm Im}w-|F(z)|^2>0\},$ where $F=(f_1,...,f_m)$ is a holomorphic map from $\mathbb{C}^n$ to $\mathbb{C}^m$, in terms of the complex singularity exponent of $F$.Comment: to appear in Science in China, a special issue dedicated to Professor Zhong Tongde's 80th birthda